Whereas adult mammalian peripheral neurons retain the capacity to regenerate injured axons, central mammalian neurons are severely limited in their regenerative growth capacity. The inability of central neurons to regenerate injured axons is due to both extrinsic and intrinsic factors. Extracellular inhibitory molecules (e.g. Nogo, MAG and OMgp) limit regeneration in the mature central nervous system (CNS). However, genetic deletion of these inhibitory molecules is insufficient for successful axonal regeneration. Manipulation of intrinsic neuronal processes can overcome these extrinsic inhibitory signals, and promote axon regeneration both in vitro and in vivo. Thus, understanding neuron-intrinsic mechanisms of axon regeneration is pivotal in the development of treatments for traumatic brain injury, spinal cord injuries, and neurodegenerative disorders.
In contrast to mature mammalian neurons, adult central neurons of some lower vertebrates and most invertebrates spontaneously regenerate following axonal injury. For instance, adult neurons of the freshwater snail Lymnaea stagnalis (L. stagnalis) have the capacity to regenerate their injured axons and re-form cell-type specific synapses, both in vitro, and in vivo. Invertebrate neurons and peripheral mammalian neurons share the capacity to locally synthesize proteins in axons and growth cones, and the identification of locally synthesized proteins has provided valuable insights into mechanisms of axon outgrowth and regeneration. Approximately 100-200 local transcripts have been reported in isolated neurites of various neuronal preparations, e.g., in Aplysia sensory neurons, in squid axoplasm and in vertebrate axons. Many of the local transcripts encode cytoskeletal proteins (e.g., microtubule, microfilament, and intermediate filament proteins), or proteins that regulate cytoskeletal dynamics (e.g., Rho and β-thymosin), suggesting that regulation of the cytoskeleton through local protein synthesis potentially serves as a conserved mechanism underlying axonal outgrowth and regeneration.
Given the need in the art for effective methods of treating nerve injury, it would be desirable to identify novel means of enhancing nerve growth and/or promoting nerve regeneration.